Hepatic steatosis estimated by VCTE-derived CAP scores was associated with lower risks of liver-related events and all-cause mortality in patients with chronic liver disease.

INTRODUCTION: The Controlled Attenuated Parameter (CAP) score derived from vibration-controlled transient elastography (VCTE, i.e. Fibroscan®) is a well-validated marker of hepatic steatosis. It is unclear if CAP scores are associated with risks of liver-related outcomes or all-cause mortality. METHODS: In this retrospective cohort study, we identified 7,587 U.S. Veterans (2,689 with cured hepatitis C [HCV], 1,523 with alcohol-associated liver disease [ALD], 3,375 with metabolic dysfunction-associated steatotic liver disease [MASLD]) who underwent VCTE between 5/2015-12/2021. We followed patients for new hepatic decompensation, hepatocellular carcinoma (HCC), and death from the VCTE date until 1/1/2022. Multivariable Cox-proportional hazards regression was used to assess for the associations between CAP measurements and clinical outcomes, adjusting for age, sex, race/ethnicity, body mass index, Charlson Comorbidity Index, diabetes, liver disease etiology, liver stiffness measurements, and FIB-4, and was reported separately by disease etiology and advanced fibrosis status. RESULTS: Over a median follow-up time of ∼1.9 years, hepatic steatosis (grades 1-3 vs. 0) was associated with a lower risk of death (aHR 0.70, 95% CI: 0.57-0.85). Among patients with MASLD, hepatic steatosis was associated with a lower risk of decompensation (aHR 0.54, 95% CI: 0.32-0.90) and death (aHR 0.52, 95% CI: 0.37-0.73). These associations persisted in subgroup analyses of patients with advanced fibrosis and without cirrhosis. DISCUSSION: Among patients who underwent VCTE in clinical practice, the presence of substantial hepatic steatosis estimated by the CAP score was associated with lower all-cause mortality among all patients and lower risk of decompensation and death among those with MASLD.

A retrospective cohort study of socioeconomic deprivation and post-liver transplant survival in adults.

The Area Deprivation Index is a granular measure of neighborhood socioeconomic deprivation. The relationship between neighborhood socioeconomic deprivation and recipient survival following liver transplantation (LT) is unclear. To investigate this, the authors performed a retrospective cohort study of adults who underwent LT at the University of Washington Medical Center from January 1, 2004, to December 31, 2020. The primary exposure was a degree of neighborhood socioeconomic deprivation as determined by the Area Deprivation Index score. The primary outcome was posttransplant recipient mortality. In a multivariable Cox proportional analysis, LT recipients from high-deprivation areas had a higher risk of mortality than those from low-deprivation areas (HR: 1.81; 95% CI: 1.03-3.18, p =0.04). Notably, the difference in mortality between area deprivation groups did not become statistically significant until 6 years after transplantation. In summary, LT recipients experiencing high socioeconomic deprivation tended to have worse posttransplant survival. Further research is needed to elucidate the extent to which neighborhood socioeconomic deprivation contributes to mortality risk and identify effective measures to improve survival in more socioeconomically disadvantaged LT recipients.

Statewide Survey of Primary Care and Subspecialty Providers on Hepatocellular Carcinoma Risk-Stratification and Surveillance Practices.

BACKGROUND: Hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis is associated with improved survival. Provision of HCC surveillance is low in the US, particularly in primary care settings. AIMS: To evaluate current hepatitis C virus (HCV) and HCC surveillance practices and physician attitudes regarding HCC risk-stratification among primary care and subspecialty providers. METHODS: Using the Tailored Design Method, we delivered a 34-item online survey to 7654 North Carolina-licensed internal/family medicine or gastroenterology/hepatology physicians and advanced practice providers in 2022. We included the domains of HCV treatment, cirrhosis diagnosis, HCC surveillance practices, barriers to surveillance, and interest in risk-stratification tools. We performed descriptive analyses to summarize responses. Tabulations were weighted based on sampling weights accounting for non-response and inter-specialty comparisons were made using chi-squared or t test statistics. RESULTS: After exclusions, 266 responses were included in the final sample (response rate 3.8%). Most respondents (78%) diagnosed cirrhosis using imaging and a minority used non-invasive tests that were blood-based (~ 15%) or transient elastography (31%). Compared to primary care providers, subspecialists were more likely to perform HCC surveillance every 6-months (vs annual) (98% vs 35%, p < 0.0001). Most respondents (80%) believed there were strong data to support HCC surveillance, but primary care providers did not know which liver disease patients needed surveillance. Most providers (> 70%) expressed interest in potential solutions to improve HCC risk-stratification. CONCLUSIONS: In this statewide survey, there were great knowledge gaps in HCC surveillance among PCPs and most respondents expressed interest in strategies to increase appropriate HCC surveillance.

Fibrosis Stage-specific Incidence of Hepatocellular Cancer After Hepatitis C Cure With Direct-acting Antivirals: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Hepatitis C virus (HCV) eradication with direct-acting antivirals reduces hepatocellular carcinoma (HCC) risk. Pooled HCC incidence rates by cirrhosis status and fibrosis stage have not been estimated using meta-analysis. METHODS: We searched PubMed, Web of Science, Embase, and Cochrane Library from January 1, 2014 to December 31, 2020 to identify studies assessing HCC incidence or outcomes by cirrhosis status, in adults with HCV who achieved sustained virologic response (SVR) after direct-acting antivirals. Pooled estimates were obtained using random-effects modeling. Subgroup, sensitivity, and meta-regression analyses were performed to evaluate heterogeneity. RESULTS: We included 31 studies involving 27,711 patients with cirrhosis (mean follow-up, 2.1 years) and 11 studies involving 32,123 patients without cirrhosis (mean follow-up, 2.6 years). HCC incidence was 2.99/100 person-years (95% confidence interval [CI], 2.52-3.54; I2 = 75%) in patients with cirrhosis, 0.47/100 person-years (95% CI, 0.32-0.70, I2 = 71%) in patients without cirrhosis, and 0.63/100 person-years (95% CI: 0.34-1.20, I2 = 0%) in stage 3 (F3) fibrosis. Among patients with cirrhosis, HCC incidence was highest in studies with <1 year of follow-up (6.17/100 person-years [95% CI, 3.73-10.19]) and progressively lower in studies with longer follow-up (1-2 years: 2.75/100 person-years [95% CI, 2.48-3.06]; 2-3 years: 2.90/100 person-years [95% CI, 1.90-4.44]; ≥3 years: 1.83/100 person-years [95% CI, 0.88-3.80]). CONCLUSION: Pooled HCC incidence after SVR in patients with cirrhosis was very high (2.99/100 person-years) but may be declining as longer time accrues after SVR. In patients without cirrhosis, including F3 fibrosis, HCC incidence was lower than thresholds associated with cost-effective HCC screening. In patients with F3 fibrosis, the lack of between-study heterogeneity provides strong evidence that HCC screening may not be warranted.

Renal Outcomes With Tenofovir Alafenamide in Liver Transplant Recipients.

Tenofovir disoproxil fumarate (TDF) is associated with a higher risk of nephrotoxicity compared with entecavir (ETV) or tenofovir alafenamide (TAF).1,2 One-fifth of transplant recipients develop chronic kidney disease (CKD) within 5 years after transplantation, contributed by the use of nephrotoxic immunosuppressive medications.3 Prior studies conducted in the nontransplant setting reported superior renal safety in TAF compared with TDF but data in liver transplant (LT) recipients have so far been limited to small case series.1,4-6 Therefore, the goals of this study were to examine changes in renal function in a large multicenter cohort of LT recipients with chronic hepatitis B who were treated with TAF, TDF, or ETV for the prevention of hepatitis B virus (HBV) reinfection or reactivation from receipt of a positive HBV core antibody graft.

Evaluating a Novel, Portable, Self-Administrable Device ("Beacon") That Measures Critical Flicker Frequency as a Test for Hepatic Encephalopathy.

INTRODUCTION: We compared critical flicker frequency (CFF) thresholds obtained using a novel portable device "Beacon" with thresholds from the commercially available Lafayette Flicker Fusion System (Lafayette-FFS) in patients with cirrhosis. METHODS: One hundred fifty-three participants with chronic liver disease underwent CFF testing using Beacon and Lafayette-FFS with a method-of-limits and/or forced-choice protocol. RESULTS: Beacon demonstrated excellent test-retest reliability (intraclass correlation 0.91-0.97) and good correlation with the Lafayette-FFS values (intraclass correlation 0.77-0.84). Forced-choice CFF were on average 4.1 Hz higher than method-of-limits descending CFFs. DISCUSSION: Beacon can be self-administered by patients with chronic liver disease and cirrhosis to measure CFF, a validated screening test for minimal hepatic encephalopathy.

Use and outcomes of hepatitis B virus-positive grafts in orthotopic liver transplantation in the United States from 1999 to 2021.

The demand for orthotopic liver transplantation (OLT) is projected to increase, which indicates a need to expand the liver donor pool. We aimed to investigate the use of hepatitis B virus (HBV)-positive grafts and the outcomes of recipients undergoing OLT with HBV-positive grafts. We conducted a retrospective cohort study analyzing all deceased donors and OLT recipients in the Organ Procurement and Transplantation Network database from January 1999 through March 2021. Donor HBV status was positive if hepatitis B surface antigen was positive or HBV nucleic acid testing was detectable. Recipients of HBV-positive allografts were matched 1:5 to recipients of HBV-negative allografts based on recipient and donor age, transplant year, recipient sex, donation after circulatory death, recipient location, and Model for End-Stage Liver Disease score at transplant. Among the 185,212 potential donors, 422 (0.2%) were HBV positive, and 265 (63%) of the HBV-positive grafts were transplanted (14 of 265 [5.3%] in HBV-positive recipients). The overall discard rate for HBV-positive donors of 37.2% (157/422) remained significantly higher than the discard rate for HBV-negative donors of 26.5% (49,026/185,212) during the study period ( p < 0.001). Recipients of HBV-positive ( n = 209) grafts had similar mortality (log-rank, p = 0.47) and graft loss (log-rank, p = 0.72) rates to the matched recipients of HBV-negative allografts ( n = 1045). The 3-year graft survival rate was 77.9% for the HBV-positive group and 79.7% in the matched HBV-negative group. Based on this analysis, transplant recipients of HBV-positive liver allografts do not experience increased rates of mortality or graft loss. One strategy that may help expand the donor pool and lower the waitlist mortality rate is using HBV-positive allografts.

Combining FIB-4 and Liver Stiffness Into the FIB-5, a Single Model that Accurately Predicts Complications of Portal Hypertension.

INTRODUCTION: We aimed to combine the fibrosis (FIB)-4 score and fibroscan-derived liver stiffness (LS) into a single score (FIB-5) that predicts incident complications of portal hypertension (PH) in persons with compensated liver disease. METHODS: In this retrospective cohort study, we identified 5849 US veterans who underwent LS measurement from May 01, 2014 to June 30, 2019, and laboratory tests enabling FIB-4 calculation within 6 months of LS measurement. Patients were followed up from the LS measurement date until February 05, 2020, for incident complications of PH. We combined LS values and the individual components of the FIB-4 score (i.e. age, aspartate aminotransferase, alanine aminotransferase, and platelet count) using multivariable Cox proportional hazards modeling and the machine learning algorithm eXtreme gradient boosting to develop the C-FIB-5 and X-FIB-5 models, respectively. Models were internally validated using optimism-corrected measures. RESULTS: Among 5,849 patients, the mean age was 62.8 years, 95.9% were men, and the mean follow-up time was 2.14 ± 1.21 years. Within 3 years after LS measurement date, 116 (2.0%) patients developed complications of PH. The X-FIB-5 (area under the receiver operating characteristic [AUROC] 0.845) and C-FIB-5 scores (AUROC 0.868) demonstrated superior discrimination over LS (AUROC 0.688) and FIB-4 (AUROC 0.672) for predicting incident complications of PH. Both the X-FIB-5 and C-FIB-5 models demonstrated higher classification accuracy across all sensitivity cutoffs when compared with LS or FIB-4 alone. DISCUSSION: We combined LS and the individual components of the FIB-4 into a single scoring system (FIB-5, www.fib5.net ), which can help identify patients with compensated liver disease at risk of developing complications of PH.

Long-term Outcomes of Pediatric Living Versus Deceased Donor Liver Transplantation Recipients: A Systematic Review and Meta-analysis.

Living donor liver transplantation (LDLT) emerged in the 1980s as a viable alternative to scarce cadaveric organs for pediatric patients. However, pediatric waitlist mortality remains high. Long-term outcomes of living and deceased donor liver transplantation (DDLT) are inconsistently described in the literature. Our aim was to systematically review the safety and efficacy of LDLT after 1 year of transplantation among pediatric patients with all causes of liver failure. We searched the MEDLINE, Medline-in-Process, MEDLINE Epub Ahead of Print, Embase + Embase Classic (OvidSP), and Cochrane (Wiley) from February 1, 1947 to February 26, 2020, without language restrictions. The primary outcomes were patient and graft survival beyond 1 year following transplantation. A meta-analysis of unadjusted and adjusted odds and hazard ratios was performed using a random-effects model. A total of 24 studies with 3677 patients who underwent LDLT and 9098 patients who underwent DDLT were included for analysis. In patients with chronic or combined chronic liver failure and acute liver failure (ALF), 1-year (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.53-0.88), 3-year (OR, 0.73; 95% CI, 0.61-0.89), 5-year (OR, 0.71; 95% CI, 0.57-0.89), and 10-year (OR, 0.42; 95% CI, 0.18-1.00) patient and 1-year (OR, 0.50; 95% CI, 0.35-0.70), 3-year (OR, 0.55; 95% CI, 0.37-0.83), 5-year (OR, 0.5; 95% CI, 0.32-0.76), and 10-year (OR, 0.26; 95% CI, 0.14-0.49) graft survival were consistently better in LDLT recipients compared with those in DDLT recipients. In patients with ALF, no difference was seen between the 2 groups except for 5-year patient survival (OR, 0.60; 95% CI, 0.38-0.95), which favored LDLT. Sensitivity analysis by era showed improved survival in the most recent cohort of patients, consistent with the well-described learning curve for the LDLT technique. LDLT provides superior patient and graft survival outcomes relative to DDLT in pediatric patients with chronic liver failure and ALF. More resources may be needed to develop infrastructures and health care systems to support living liver donation.

Association of Donor and Recipient Cytomegalovirus Serostatus on Graft and Patient Survival in Liver Transplant Recipients.

Among solid organ transplant recipients, donor cytomegalovirus (CMV) seropositive (D+) and recipient seronegative (R-) status are associated with an increased risk of graft loss and mortality after kidney or lung transplantation. Whether a similar relationship exists among liver transplant recipients (LTR) is unknown. We assessed graft loss and mortality among adult LTRs from January 1, 2010, to March 14, 2020, in the Organ Procurement and Transplantation Network database. We used multivariable mixed Cox proportional hazards regression to analyze the association of donor and recipient CMV serostatus group with graft loss and mortality, with donor seronegative (D-) and recipient seronegative (R-) as the reference group. Among 54,078 LTRs, the proportion of D-R-, D- and recipient seropositive (R+), D+R-, and D+R+ was 13.4%, 22.5%, 22%, and 42%, respectively. By unadjusted Kaplan-Meier survival curve estimates, survival by the end of follow-up was 73.3%, 73.5%, 70.1%, and 69.7%, among the D-R-, D-R+, D+R-, and D+R+ groups, respectively. By multivariable Cox regression, the CMV D+R- serogroup, but not other serogroups, was independently associated with increased risks of graft loss (adjusted hazard ratio [aHR], 1.13; 95% confidence interval [CI], 1.05-1.22) and mortality (aHR, 1.13; 95% CI, 1.05-1.22). The magnitude of the association of the CMV D+R- serostatus group with mortality was similar when the Cox regression analysis was restricted to the first year after transplant and beyond the first year after transplant: aHR, 1.13 (95% CI, 1.01-1.27) and aHR, 1.13 (95% CI, 1.02-1.25), respectively. Even in an era of CMV preventive strategies, CMV D+R- serogroup status remains independently associated with increased graft loss and mortality in adult LTRs. Factors in addition to direct CMV-associated short-term mortality are likely, and studies to define the underlying mechanism(s) are warranted.

Nonalcoholic Fatty Liver Disease Risk Factors Affect Liver-Related Outcomes After Direct-Acting Antiviral Treatment for Hepatitis C.

INTRODUCTION: In hepatitis C (HCV) patients, obesity and/or diabetes may increase the risk of liver-related outcomes. We aimed to determine whether diabetes and/or obesity are associated with adverse outcomes in direct-acting antiviral (DAA)-treated HCV patients. METHODS: We conducted a retrospective study of 33,003 HCV-infected, DAA-treated Veterans between 2013 and 2015. Body mass index was used to categorize patients into underweight (< 18.5 kg/m2), normal weight (18.5 to < 25 kg/m2), overweight (25 to < 30 kg/m2), obesity I (30 to < 35 kg/m2), and obesity II-III (> 35 kg/m2). Diabetes was defined by ICD-9/10 codes in association with hemoglobin A1c > 6.5% or medication prescriptions. Patients were followed from 180 days post-DAA initiation until 2/14/2019 to assess for development of cirrhosis, decompensations, hepatocellular carcinoma (HCC), and death. Multivariable Cox proportional hazards regression models were used to determine the association between diabetes and/or obesity and outcomes. RESULTS: During a mean follow-up of 3 years, 10.1% patients died, 5.0% were newly diagnosed with cirrhosis, 4.7% had a decompensation and 4.0% developed HCC. Diabetes was associated with an increased risk of mortality (AHR = 1.25, 95% CI 1.10-1.42), cirrhosis (AHR = 1.31, 95% CI 1.16-1.48), decompensation (AHR = 1.74, 95% CI 1.31-2.31), and HCC (AHR = 1.32, 95% CI 1.01-1.72) among patients without baseline cirrhosis. Compared to normal-weight persons, obese persons had a higher risk of cirrhosis, but overweight and obese persons had lower risk of mortality and HCC. CONCLUSIONS: In this large DAA-treated Veterans cohort, pre-DAA diabetes increases mortality and liver-related events independent of SVR. Continued vigilance is warranted in patients with diabetes despite SVR. Elevated BMI categories appear to have improved outcomes, although further studies are needed to understand those associations.

A Simple Measure of Hepatocellular Carcinoma Burden Predicts Tumor Recurrence After Liver Transplantation: The Recurrent Hepatocellular Carcinoma-Initial, Maximum, Last Classification.

Risk of recurrent hepatocellular carcinoma (rHCC) after liver transplantation (LT) depends on the pre-LT HCC burden, tumor behavior, and response to locoregional therapy (LRT). In December 2017, LT priority for HCC was expanded to select patients outside the Milan criteria who respond to LRT. Our aims were to develop a novel objective measure of pre-LT HCC burden (model of recurrent hepatocellular carcinoma-initial, maximum, last [RH-IML]), incorporating tumor behavior over time, and to apply RH-IML to model post-LT rHCC. Using United Network for Organ Sharing data from between 2002-2014 (development) and 2015-2017 (validation), we identified adult LT recipients with HCC and assessed pre-LT HCC tumor behavior and post-LT rHCC. For each patient, HCC burden was measured at 3 points on the waiting list: initial (I), maximum (M) total tumor diameter, and last (L) exception petition. HCC burden at these 3 points were classified as (A) Milan to University of California, San Francisco (UCSF), and (D) >UCSF, resulting in each patient having a 3-letter RH-IML designation. Of 16,558 recipients with HCC, 1233 (7%) had any post-LT rHCC. rHCC rates were highest in RH-IML group CCC (15%) and DDD (18%). When M and L tumor burdens did not exceed Milan (class B or A), rHCC was low (≤10%) as in AAA, ABA, ABB, BBA, BBB; rHCC was also low (≤10%) with successful downstaging when L was A (

Utilization of Census Tract-Based Neighborhood Poverty Rates to Predict Non-adherence to Screening Colonoscopy.

OBJECTIVES: Efforts to improve colorectal cancer (CRC) screening rates include recognizing predictors of colonoscopy non-adherence and identifying these high-risk patient populations. Past studies have focused on individual-level factors but few have evaluated the influence of neighborhood-level predictors. We sought to assess the effect of census tract-based neighborhood poverty rates on scheduled screening colonoscopy non-adherence. METHODS: In this prospective observational cohort study, data from electronic medical records and appointment tracking software were collected in 599 patients scheduled to undergo outpatient CRC screening colonoscopy at two academic endoscopy centers between January 2011 and December 2012. Non-adherence was defined as failure to attend a colonoscopy appointment within 1 year of the date it was electronically scheduled. Neighborhood poverty rate was determined by matching patients' self-reported home address with their corresponding US census tract. Individual factors including medical comorbidities and prior appointment adherence behavior were also collected. RESULTS: Overall, 17% (65/383) of patients were non-adherent to scheduled colonoscopy at 1-year follow-up. Neighborhood poverty rate was a significant predictor of non-adherence to scheduled screening colonoscopy in multivariate modeling (OR 1.53 per 10% increase in neighborhood poverty rate, 95% CI 1.21-1.95, p < 0.001). By incorporating the neighborhood poverty rate, screening colonoscopy non-adherence was 31% at the highest quartile compared to 14% at the lowest quartile of neighborhood poverty rates (p = 0.006). CONCLUSIONS: Census tract-based neighborhood poverty rates can be used to predict non-adherence to scheduled screening colonoscopy. Targeted efforts to increase CRC screening efficiency and completion among patients living in high-poverty geographic regions could reduce screening disparities and improve utilization of endoscopy unit resources.

Meta-analysis: superior treatment response in Asian patients with hepatitis C virus genotype 6 versus genotype 1 with pegylated interferon and ribavirin.

OBJECTIVE: Our goal was to systematically and quantitatively assess treatment response between Asian patients with hepatitis C virus genotype 6 (HCV-6) and hepatitis C virus genotype 1 (HCV-1) treated for 48 weeks with pegylated interferon and ribavirin. METHODS: We performed a literature search in MEDLINE and EMBASE for 'genotype 6' in August 2013. Additional abstracts from major international scientific conferences from 2012 to 2013 were reviewed. Studies included were original articles with ≥10 treatment-naïve Asian HCV-6 patients. Exclusion criteria were coinfections with hepatitis B virus, HIV and/or other liver diseases. Heterogeneity was defined as a Cochrane Q test with a p value of 0.10 and an I(2) statistic of >50%. RESULTS of a random-effects model are reported. RESULTS: A total of 1,046 (503 HCV-6; 543 HCV-1) patients from 12 studies were included in the analysis. The pooled sustained virologic response (SVR) rate was 80.2% (95% CI 74.3-85.0, Q statistic = 20.87, p < 0.035; I(2) = 47.3%) for HCV-6 and 62.5% (95% CI 41.9-79.4, Q statistic = 52.41, p < 0.001; I(2) = 92.37) for HCV-1 patients. HCV-6 patients had a significantly higher SVR rate compared to HCV-1 patients (odds ratio 2.73, 95% CI 1.69-4.41, p < 0.001). Approximately one fourth of patients without early virologic response (EVR) achieved SVR, regardless of genotype (HCV-1, n = 6/23; HCV-6, n = 4/21). CONCLUSIONS: Asian patients with HCV-6 can expect higher SVR rates (∼80%) than HCV-1 patients (∼63%). EVR as a stopping rule is less clear in Asian patients with HCV-6 and HCV-1.

Poor Sustained Virological Response in a Multicenter Real-Life Cohort of Chronic Hepatitis C Patients Treated with Pegylated Interferon and Ribavirin plus Telaprevir or Boceprevir.

BACKGROUND: There are limited data analyzing the effectiveness of boceprevir (BOC) or telaprevir (TVR) in combination with pegylated interferon (PEG-IFN) plus ribavirin (RBV) in a real-life patient cohort. AIMS: In clinical trials, patients with chronic hepatitis C (CHC) treated with BOC or TVR plus PEG-IFN and RBV achieved sustained virological response (SVR) rates of 70 %. However, it is not clear whether similar results can be realized in routine practice. Our goal is to examine SVR rates of these triple regimens for CHC in a multicenter real-life patient cohort. METHODS: We retrospectively studied 200 consecutive CHC genotype 1 patients who were initiated on PEG-IFN, RBV, and either TVR (n = 113) or BOC (n = 87) from July 2011 to February 2014 at two US academic liver clinics, a Veterans Affairs liver clinic and a community gastroenterology clinic. RESULTS: Both BOC and TVR treatment groups were similar in regard to comorbidities, BMI, and HCV RNA levels. BOC patients were more likely to have cirrhosis than TVR patients (47 vs. 24 %, P = 0.001). SVR rates were low in both cohorts (40 % for BOC, 53 % for TVR, P = 0.05). On multivariate logistic regression, treatment adherence by the "80/80/80 rule," diagnosis of cirrhosis, and use of erythropoietin were statistically significant predictors for SVR. Of these, treatment adherence was the strongest predictor (OR 4.43, 95 % CI 2.8-6.06, P < 0.001). CONCLUSION: SVR was much lower in a real-life patient cohort than in clinical trials (53 % for TVR and 40 % for BOC, compared to 66-75 % in clinical trials).

Mutations in HBV DNA polymerase associated with nucleos(t)ide resistance are rare in treatment-naive patients.

BACKGROUND & AIMS: Prior studies have detected hepatitis B virus (HBV) DNA polymerase mutations in treatment-naive patients. However, most of these studies used either direct polymerase chain reaction sequencing, which detects these mutations with low levels of sensitivity, or patient cohorts that were not well-characterized. We investigated the prevalence of HBV mutations in DNA polymerase by using a line probe assay. METHODS: In a prospective, cross-sectional study, we enrolled 198 treatment-naive patients with chronic hepatitis B (52.5% male; mean age, 41 years) from February 2009 to May 2011 from 3 gastroenterology and liver clinics in Northern California. Exclusion criteria included infection with hepatitis C or D viruses or human immunodeficiency virus. All patients completed a questionnaire (to determine demographics, history of liver disease, prior treatments, family medical history, drug and alcohol use, and environmental risk factors for hepatitis) that was administered by a research coordinator; mutations in HBV DNA polymerase were detected by using the INNO-LiPA HBV DR v.3 assay. RESULTS: Most patients were Vietnamese (48.5%) or Chinese (36.4%) and were infected with HBV genotypes B (67.5%) or C (24.2%). Mutations in HBV DNA polymerase were found in 2 patients (1%), rtI233V (n = 1) and rtM250M/L (n = 1). CONCLUSIONS: In a multicenter prospective study of treatment-naive patients with chronic hepatitis B, we detected mutations in HBV DNA polymerase in only 1%. Because of the low prevalence of these mutations and the uncertain clinical significance of such quasispecies, routine HBV DNA polymerase mutation analysis cannot be recommended before initiation of antiviral therapy for treatment-naive patients with chronic hepatitis B. The analysis requires further molecular and clinical studies.

Screening for Hepatocellular Carcinoma and Survival in Patients With Cirrhosis After Hepatitis C Virus Cure.

Importance: The risk of hepatocellular carcinoma (HCC) declines over time after hepatitis C virus (HCV) cure by direct-acting antiviral (DAA) therapies. Liver society guidelines recommend continuing HCC screening for these patients, but data on screening outcomes are lacking. Objective: To evaluate the association of HCC screening after HCV cure with overall survival. Design, Setting, and Participants: This cohort study evaluated patients with HCV cirrhosis who achieved DAA-induced HCV cure in the Veterans Affairs health care system between January 2014 and December 2022. Data analysis occurred from October 2023 to January 2024. Exposures: The percentage of time spent up to date with recommended HCC screening was calculated by year of follow-up and during the 4 years preceding HCC diagnosis (the detectable asymptomatic phase). Main Outcomes and Measures: The primary outcome was overall survival after HCC diagnosis and was compared by percentage of time spent up to date with screening using Kaplan-Meier analyses and Cox proportional hazards regression. Early-stage HCC at diagnosis and curative treatment were secondary outcomes assessed using logistic regression. Results: A total of 16 902 individuals were included (median [IQR] age, 64.0 [60.5-67.4] years; 16 426 male [97.2%]), of whom 1622 developed HCC. The cumulative incidence of HCC declined from 2.4% (409 of 16 902 individuals) to 1.0% (27 of 2833 individuals) from year 1 to year 7 of follow-up. Being up to date with screening for at least 50% of time during the 4 years preceding HCC diagnosis was associated with improved overall survival (log-rank test of equality over strata P = .002). In multivariate analysis, each 10% increase in follow-up spent up to date with screening was associated with a 3.2% decrease in the hazard of death (hazard ratio, 0.97; 95% CI, 0.95-0.99). There was a statistically significant interaction between time since HCV cure and screening, with no association observed among those who received a diagnosis of HCC more than 5 years after HCV cure. Each 10% of time spent up to date with screening was associated with a 10.1% increased likelihood of diagnosis with early-stage HCC (95% CI, 6.3%-14.0%) and a 6.8% increased likelihood of curative treatment (95% CI, 2.8%-11.0%). Conclusions and Relevance: In this cohort study of persons with HCV-related cirrhosis who achieved HCV cure and subsequently developed HCC, remaining up to date with screening was associated with improved overall survival, supporting the screening of eligible individuals.

Hepatocellular carcinoma risk decreases as time accrues following hepatitis C virus eradication.

BACKGROUND: It is unclear whether the risk of hepatocellular carcinoma (HCC) decreases over time following hepatitis C virus (HCV) eradication. AIM: To determine if patients who have accrued longer time since sustained virologic response (SVR) have a lower risk of HCC than those with less time since SVR METHODS: We conducted a retrospective cohort study of all HCV-infected Veterans Affairs patients who achieved SVR before 1 January 2018 and remained alive without a diagnosis of HCC as of 1 January 2019 (n = 75,965). We ascertained their baseline characteristics as of 1 January 2019 (time zero), including time accrued since SVR and followed them for the subsequent 12 months for incident HCC. We used multivariable Cox proportional hazards regression to determine the association between time since SVR and HCC risk after adjusting for age, race/ethnicity, sex, diabetes, hypertension, body mass index, alcohol use, Charlson Comorbidity Index, Fibrosis-4 score, HCV genotype, hepatitis B virus co-infection and HIV co-infection. RESULTS: 96.0% were male; mean age was 64.6 years. Among those with cirrhosis (n = 19,678, 25.9%), compared to patients who had accrued only ≥1 to 2 years since SVR (HCC incidence 2.71/100 person-years), those who had accrued >2 to 4 years (2.11/100 person-years, aHR 0.80, 95% CI 0.63-1.01) and >4 to 6 years (1.65/100 person-years, aHR 0.61, 95% CI 0.41-0.90) had progressively lower HCC risk. However, HCC risk appeared to plateau for those with >6 years since SVR (1.68/100 person-years, aHR 0.70, 95% CI 0.46-1.07). Among those without cirrhosis, HCC risk was 0.23-0.27/100 person-years without a significant association between time since SVR and HCC risk. CONCLUSIONS: Among patients with cirrhosis and cured HCV infection, HCC risk declined progressively up to 6 years post-SVR-although it remained well above thresholds that warrant screening. This suggests that time since SVR can inform HCC surveillance strategies in patients with cured HCV infection and can be incorporated into HCC risk prediction models.

Increasing Proportion of High-risk Cytomegalovirus Donor-positive/Recipient-negative Serostatus in Solid Organ Transplant Recipients.

BACKGROUND: Cytomegalovirus (CMV) donor-positive/recipient-negative (D+R-) serostatus is independently associated with worse allograft and patient survival across solid organ transplant (SOT) types. We characterized trends in CMV D+R- serostatus among adult SOT recipients performed in the United States. METHODS: Donor (D) and recipient (R) CMV serostatus and demographic factors were obtained from the Scientific Registry of Transplant Recipients for persons ≥18 y undergoing a first SOT between January 1, 2000, and December 31, 2020. The proportions of D+R- SOTs over time were assessed using Chi square for trend and modeled through 2040. Factors associated with D/R seropositivity were assessed using logistic models. RESULTS: Among 472 549 SOTs, the average proportion of D+R- SOTs increased significantly among kidney, liver, heart, and lung between 2000 to 2009 and 2010 to 2020: 18.0% to 18.3% ( P = 0.034), 19.4% to 21.8% ( P < 0.001), 22.2% to 25.5% ( P < 0.001), and 23.6% to 27.0% ( P < 0.001), respectively. The increased proportion over time resulted from a disproportionate increase in R- (34.9% to 37.0% for all organ types, P < 0.001) and a smaller corresponding change in D+ (60.8% to 60.3%, P < 0.001). CONCLUSIONS: The proportion of high-risk CMV D+R- SOTs increased significantly across all organs and is projected to continue to increase. These findings inform population-level strategies to mitigate the negative impact of CMV D+R- in SOT.